Abstract

Background

Pyronaridine, a Mannich base anti-malarial with high efficacy against drug resistant
Plasmodium falciparum, is currently evaluated as a fixed dose combination with artesunate for the treatment
of uncomplicated malaria. In this study, the in vitro activity of pyronaridine against clinical isolates of P. falciparum from Lambaréné, Gabon, was assessed in order to obtain baseline data on its activity
prior to its future use in routine therapy. Moreover, follow-up assessment on the
in vitro activity of chloroquine, artesunate and quinine was performed.

Methods

In vitro response of field isolates of P. falciparum to pyronaridine, chloroquine, artesunate and quinine was assessed using the traditional
WHO microtest. In addition, the histidine-rich protein 2 (HRP-2) assay was performed
and evaluated for its future implementation for follow-up of drug susceptibility testing.

Results

Pyronaridine exhibited a high in vitro activity against P. falciparum, with a geometric mean cut-off concentration of 9.3 nmol/l. Fifty percent effective
concentrations were 1.9 nmol/l and 2.0 nmol/l in the WHO microtest and HRP-2 assay,
respectively. Results matched closely in vivo findings from a recent clinical trial on pyronaridine-artesunate treatment. One isolate
showed diminished sensitivity to artesunate. For chloroquine and quinine resistance
levels were comparable to prior studies from Lambaréné. Results from the novel HRP-2
assay corresponded well to those obtained by the WHO microtest.

Conclusion

Pyronaridine is highly active in chloroquine-resistant parasites and seems a promising
partner drug for artemisinin-based combination therapy in Africa.